Articles: hyperalgesia.
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Ann. N. Y. Acad. Sci. · Mar 2001
ReviewSpinal cord neuroplasticity following repeated opioid exposure and its relation to pathological pain.
Convincing evidence has accumulated that indicates neuroplastic changes within the spinal cord in response to repeated exposure to opioids. Such neuroplastic changes occur at both cellular and intracellular levels. It has been generally acknowledged that the activation of N-methyl-D-aspartate (NMDA) receptors plays a pivotal role in the development of neuroplastic changes following repeated opioid exposure. ⋯ Interestingly, similar cellular and intracellular changes occur in the spinal cord following peripheral nerve injury. These findings indicate that interactions exist in the spinal cord neural structures between two seemingly unrelated conditions-chronic opioid exposure and a pathological pain state. These observations may help understand mechanisms of chemical intolerance and multiple chemical sensitivity as well as have significant clinical implications in pain management with opioid analgesics.
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Randomized Controlled Trial Clinical Trial
Concentration-effect relationship of intravenous alfentanil and ketamine on peripheral neurosensory thresholds, allodynia and hyperalgesia of neuropathic pain.
Both mu opioid agonists and N-methyl-D-aspartate (NMDA) receptor antagonists are implicated in the regulation of neuropathic pain in post-nerve injury preclinical pain models. This study characterizes the effects of intravenously infused alfentanil (a mu-receptor agonist) and ketamine (an NMDA-receptor antagonist) on human neuropathic pain states, characterized by allodynia and hyperalgesia. Using diphenhydramine as the placebo, alfentanil and ketamine infusions were given in a randomized double-blind fashion 1 week apart via a computer-controlled infusion (CCI) pump that was programmed to target plasma levels of alfentanil at 25, 50 and 75 ng/ml and ketamine at 50, 100 and 150 ng/ml. ⋯ Therefore, clinical utilization of opioids with careful titration may be beneficial in post-nerve injury patients with partial deafferentation. With the absence of significant CNS side effects, the ketamine infusion not only demonstrated the well-documented spinal cord mechanism of the NMDA receptor, but the result of the current study also suggests that a peripheral mechanism of NMDA receptor may exist. The relationship between central sensitization and regulation of peripheral NMDA-receptor expression requires further investigation.
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The traditional specificity theory of pain perception holds that pain involves a direct transmission system from somatic receptors to the brain. The amount of pain perceived, moreover, is assumed to be directly proportional to the extent of injury. Recent research, however, indicates far more complex mechanisms. ⋯ It is clear from the material presented that the perception of pain does not simply involve a moment-to-moment analysis of afferent noxious input, but rather involves a dynamic process that is influenced by the effects of past experiences. Sensory stimuli act on neural systems that have been modified by past inputs, and the behavioral output is significantly influenced by the "memory" of these prior events. An increased understanding of the central changes induced by peripheral injury or noxious stimulation should lead to new and improved clinical treatment for the relief and prevention of pathological pain.
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J. Pharmacol. Exp. Ther. · Mar 2001
Antinociceptive effects of delta-opioid agonists in Rhesus monkeys: effects on chemically induced thermal hypersensitivity.
The effects of SNC80 and other structurally related delta-opioid receptor agonists were assessed under conditions of chemically induced hypersensitivity to thermal stimuli in four rhesus monkeys. The shaved tail of each monkey was exposed to warm water (38, 42, 46, and 50 degrees C), and the tail-withdrawal latency from each temperature was recorded. The effects of drugs on the temperature that produced a 10-s tail-withdrawal latency (the T(10) value) were examined. ⋯ In contrast, neither SNC67 (10.0 mg/kg), which is the (-)-enantiomer of SNC80, nor the nonsteroidal anti-inflammatory drug (NSAID) ketorolac (1.0-10.0 mg/kg) modified the effects of capsaicin. SNC80 was also effective in reversing thermal hypersensitivity induced by prostaglandin E(2) (0.0158 mg) and Freund's complete adjuvant (10% concentration). These findings suggest that delta-agonists have antinociceptive effects in primates under conditions of chemically induced thermal hypersensitivity and might be effective under a broader range of conditions than clinically available NSAIDs.
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We have examined the effects of a novel GABA(B) agonist, CGP35024, in models of chronic neuropathic (partial sciatic ligation) and inflammatory (Freund's complete adjuvant) pain in the rat, and its inhibitory action on spinal transmission in vitro. The effects of CGP35024 were compared with L-baclofen and gabapentin. CGP35024 and L-baclofen reversed neuropathic mechanical hyperalgesia following single subcutaneous or intrathecal administration, but did not affect inflammatory mechanical hyperalgesia. ⋯ In the isolated hemisected spinal cord from the rat, CGP35024, L-baclofen and gabapentin all inhibited capsaicin-evoked ventral root potentials (VRPs). CGP35024 and L-baclofen, but not gabapentin, also inhibited the polysynaptic and monosynaptic phases of electrically-evoked VRPs, as well as the 'wind-up' response to repetitive stimulation. These data indicate that CGP35024 and L-baclofen modulate nociceptive transmission in the spinal cord to inhibit neuropathic hyperalgesia, and that CGP35024 has a therapeutic window for antihyperalgesia over spasmolysis.